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Abstract Background Despite the growing interest in the use of human genomic data for drug target identification and validation, the extent to which the spectrum of human disease has been addressed by genome-wide association studies (GWAS), or by drug development, and the degree to which these efforts overlap remain unclear. Methods In this study we harmonize and integrate different data sources to create a sample space of all the human drug targets and diseases and identify points of convergence or divergence of GWAS and drug development efforts. Results We show that only 612 of 11,158 diseases listed in Human Disease Ontology have an approved drug treatment in at least one region of the world. Of the 1414 diseases that are the subject of preclinical or clinical phase drug development, only 666 have been investigated in GWAS. Conversely, of the 1914 human diseases that have been the subject of GWAS, 1121 have yet to be investigated in drug development. Conclusions We produce target-disease indication lists to help the pharmaceutical industry to prioritize future drug development efforts based on genetic evidence, academia to prioritize future GWAS for diseases without effective treatments, and both sectors to harness genetic evidence to expand the indications for licensed drugs or to identify repurposing opportunities for clinical candidates that failed in their originally intended indication.

Background and objective: The progression of chronic kidney disease (CKD) involves the development of alterations in mineral metabolism that are closely related to cardiovascular outcomes and bone disease. Hypomagnesemia is associated with more rapid progression of CKD and other comorbidities. Our objective was to analyze in CKD patients stages 3–4 the impact of the administration of magnesium (Mg) carbonate on bone mineral density (BMD) and hemodynamic changes associated with by vascular calcification (VC). Material and methods: Patients with CKD stages 3–4 were randomized into controls (n = 12) or intervention (n = 7) group receiving 360 mg of Mg carbonate daily during a 15-month period. Parameters related to mineral metabolism, BMD, VC, and pulse wave velocity (PWV) were evaluated. Results: Supplementation with Mg produced an increase in the urinary excretion of Mg while serum Mg levels remained stable and no episodes of hypermagnesemia were reported. In addition, no significant changes were found in the degree of VC assessed by Adragao index, however, both serum and urine Mg were significantly associated with a decrease in PWV, suggesting an increase in vascular compliance. Likewise, BMD did not change following treatment, but serum Mg significantly correlated with the levels of N-terminal propeptide of collagen alpha-1(I) chain (PINP), a marker of bone synthesis. Conclusions: In sum, these results suggest a possible beneficial effect of Mg on vascular compliance with no detrimental effects on bone status. In addition, our results highlight the need to consider monitorization of urinary Mg status in CKD patients. Resumen: Antecedentes y objetivos: La progresión de la enfermedad renal crónica (ERC) supone el desarrollo de alteraciones del metabolismo mineral que están estrechamente relacionadas con eventos cardiovasculares y enfermedad ósea. La hipomagnesemia se asocia con una progresión más rápida de la ERC, así como con otras comorbilidades. Nuestro objetivo fue analizar en pacientes con ERC estadios 3-4 el impacto de la administración de carbonato de magnesio (Mg) sobre la densidad mineral ósea (DMO) y los cambios hemodinámicos asociados a la calcificación vascular (CV). Material y métodos: Los pacientes con enfermedad renal crónica estadios 3-4 se distribuyeron aleatoriamente en los grupos control (n=12) o intervención (n=7), que recibió 360 mg de carbonato de Mg diariamente durante un periodo de 15 meses. Se evaluaron parámetros relacionados con el metabolismo mineral además de la DMO, CV, y velocidad de onda de pulso (VOP). Resultados: La suplementación con Mg produjo un aumento en la excreción urinaria de Mg, mientras que los niveles séricos de Mg permanecieron estables y no se reportaron episodios de hipermagnesemia. Además, no se observaron cambios significativos en cuanto al grado de CV valorado en base al índice de Adragao. No obstante, tanto los niveles séricos como urinarios de Mg se asociaron significativamente con un descenso en la VOP, lo que sugiere un aumento en la distensibilidad vascular. De manera similar, la DMO no se modificó con la administración del tratamiento, pero los niveles séricos de Mg correlacionaron significativamente con los del propétido N-terminal del colágeno tipo I (PINP), un marcador de la síntesis ósea. Conclusiones: En conjunto, estos resultados sugieren un posible efecto beneficioso del Mg sobre la distensibilidad vascular sin efectos negativos a nivel óseo. Además, nuestros resultados subrayan la necesidad de considerar la monitorización del nivel de Mg urinario en pacientes con ERC.

Faced with the ecological crisis, environmental scientists are asking what else besides providing evidence can they do to steer needed processes of substantive change. We argue that such an exploration should start by recognizing their weakness regarding the forces aiming at slowing down the pace of change. Recognizing this weakness should lead scientists to a change of tactics, embracing forms of strategic action used for centuries by groups on the weaker side of power struggles: that is, guerrilla strategies. Avoiding simplistic celebrations of guerrillas—historically a form of warfare that has produced as much pain as gain—an appraisal of some of its strategic tenets could help scientists to sketch alternative forms of engagement with the ecological crisis. Instead of grand gestures and direct confrontations, they could focus on carrying out epistemic strategic actions, or initiatives centered on the strategic usage of environmental knowledge and knowledge infrastructures to reduce, neutralize, and/or redress the impact of the organizations and regulations blocking, diverting, or slowing down decisive action regarding the ecological crisis. These actions could involve producing novel forms of knowledge, exposing facts that are currently hidden, refusing to engage in the production of contentious knowledge or, in extreme cases, disrupting specially damaging knowledge infrastructures. Please refer to Supplementary Material for a full text Spanish version of this article. Ante la gravedad de la crisis ecológica, científicos de distintas áreas se están preguntando qué más podemos hacer -además de aportar evidencia- para motivar procesos sustantivos de transformación socioambiental. En este artículo, sostenemos que la exploración de formas alternativas de acción debería empezar por reconocer la posición de debilidad de los científicos frente a las fuerzas que buscan ralentizar o frenar los procesos de transformación. Reconocer esta debilidad debería llevarnos a un cambio de táctica, adoptando formas de acción estratégica utilizadas durante siglos por grupos en el lado más débil de las luchas de poder: las guerrillas. Evitando una celebración simplista de la guerrilla -históricamente una forma de conflicto armado que ha producido más dolor que logros- analizamos cómo algunos de sus principios estratégicos nos pueden servir para desde las ciencias esbozar formas alternativas de acción en relación con la crisis ecológica. En lugar de declaraciones públicas y enfrentamientos directos, los científicos deberíamos desarrollar novedosas acciones epistémicas estratégicas, es decir, iniciativas centradas en el uso estratégico del conocimiento ambiental y sus infraestructuras para reducir, neutralizar y/o corregir el impacto de organizaciones y normativas que bloquean, desvían o ralentizan las transformaciones urgentes en relación con la crisis ecológica. Estas acciones podrían implicar la producción de formas novedosas de conocimiento, la exposición de conocimiento actualmente oculto, la negativa a participar en la producción de conocimiento controversial o, en casos extremos, la disrupción de infraestructuras o procesos de conocimiento especialmente dañinos. La versión en español de este artículo se puede encontrar en Material Suplementarias.

Summary: Background: Ultraviolet- C (UV–C) light is effective for reducing environmental bioburden in hospitals, and the use of robots to deliver it may be advantageous. Aim: To evaluate the feasibility and clinical efficacy of an autonomous programmable UV-C robot in surgical and intensive care unit (ICU) rooms of a tertiary hospital. Method: During ten consecutive months, the device was used in six theatres where cardiac, colorectal and orthopaedic surgeries were performed, and in the rooms previously occupied by patients subjected to contact precautions of a 14-bed ICU. Surgical site infection (SSI) rates of procedures performed in the UV-cleaned theatres were compared with those of the previous year. Incidence in clinical samples of ICU-acquired multiple-drug resistant (MDR) microorganisms was compared with that of the same period of the previous year. An UV-C exposure study done by semi-quantitative dosimeters and a survey of the bioburden on surfaces were carried out. Findings: SSI rates in the pre- and post-intervention periods were 8.67% (80/922) and 7.5% (61/813), respectively (p=0.37). Incidence of target microorganisms in clinical samples remained unchanged (38.4 vs. 39.4 per 10,000 patient-days, p=0.94). All the dosimeters exposed to ≤1 meter received ≥500 mJ/cm2. The bacterial load on surfaces decreased after the intervention, particularly in ICU rooms (from 4.57±7.4 CFU to 0.27±0.8 CFU, p

Early detection of disseminating vancomycin-resistant Enterococcus faecium (VREfm) in ICU wards is crucial for outbreak identification and the implementation of prompt infection control measures. Genotypic methods like pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS) are costly and time-consuming, hindering rapid response due to batch dependency. Fourier-transform infrared spectroscopy (FT-IR) offers the potential for real-time outbreak detection and reliable strain typing. We utilized FT-IR to identify clonal VREfm dissemination and compared its performance to PFGE and WGS. Between February through October 2023, an unusually high number of VREfm were recovered at a tertiary hospital in Barcelona. Isolates were examined for antimicrobial susceptibility, carriage of vanA/vanB genes and clonality was also studied using FT-IR, PFGE, and WGS. Routine FT-IR inspections revealed recurring VREfm clustering during the outbreak's initial weeks. In total, 104 isolates were recovered from 75 patients and from multiple wards. However, only one isolate was recovered from an environmental sample, suggesting the absence of environmental reservoirs. An ST80 vancomycin-resistant (vanA) E. faecium strain was the main strain responsible for the outbreak, although a few additional VREfm strains were also identified, all belonging to CC17. PFGE and cgMLST (WGS) yielded identical clustering results to FT-IR, and WGS confirmed vanA/vanB gene carriage in all VREfm isolates. Infection control measures led to a rapid decline in VREfm isolates, with no isolates detected in November. FT-IR spectroscopy offers rapid turnaround times, sensitivity, and reproducibility, comparable to standard typing methods. It proved as an effective tool for monitoring VREfm dissemination and early outbreak detection.

Objectives Assessment of age, sex and smoking-specific risk of cancer diagnosis and non-cancer mortality following primary care consultation for 15 new-onset symptoms.Methods and analysis Data on patients aged 30–99 in 2007–2017 were extracted from a UK primary care database (CPRD Gold), comprising a randomly selected reference group and a symptomatic cohort of patients presenting with one of 15 new onset symptoms (abdominal pain, abdominal bloating, rectal bleed, change in bowel habit, dyspepsia, dysphagia, dyspnoea, haemoptysis, haematuria, fatigue, night sweats, weight loss, jaundice, breast lump and post-menopausal bleed).Time-to-event models were used to estimate outcome-specific hazards for site-specific cancer diagnosis and non-cancer mortality and to estimate cumulative incidence up to 12 months following index consultation.Results Data included 1 622 419 patients, of whom 36 802 had a cancer diagnosis and 28 857 died without a cancer diagnosis within 12 months of the index.The risk of specific cancers exceeded the UK urgent referral risk threshold of 3% from a relatively young age for patients with red flag symptoms. For non-organ-specific symptoms, the risk of cancer at individual sites either did not reach the threshold at any age or reached it only in older patients.Conclusion Patients with new-onset symptoms in primary care often have comparable risks of cancer diagnosis and non-cancer mortality. Non-organ-specific symptoms, in particular, are associated with elevated risk of cancer at multiple different sites. Management of symptomatic patients in primary care should be informed by the risk of different cancer types alongside mortality risk.

Background Idiopathic pulmonary fibrosis (IPF) is a rare disorder associated with increased mortality and morbidity. There are currently two drugs approved for IPF but their safety and efficacy profile in real-world settings in Spain is not well understood.Methods An observational, multicentre, prospective study was carried out among patients with IPF who started treatment with pirfenidone or nintedanib from 2015 to 2021. Data regarding clinical characteristics, drug adherence, safety profiles and clinical outcomes between these two drugs were collected.Results 232 patients were included in the analysis. There were no meaningful differences between both groups at baseline. Patients who started pirfenidone showed a decreased risk for treatment withdrawal compared with those starting nintedanib (HR 0.65 (95% CI 0.46 to 0.94; p=0.002)). Time to first adverse event and all-cause mortality was similar between study groups. Risk factors for withdrawal were female sex, diarrhoea and photosensitivity.Conclusions in this real-world study, both pirfenidone and nintedanib showed similar efficacy profiles. Pirfenidone was associated with less treatment discontinuations due to side effects.

Introdução e objetivo: A obesidade é uma doença crônica não transmissível, considerada pela Organização Mundial de Saúde uma epidemia mundial. A Cirurgia Bariátrica (CB) é uma alternativa do tratamento da obesidade. Além dos impactos físicos, a obesidade acarreta também impacto psicológico, que reflete de forma negativa na vida do indivíduo, e pode persistir ou se intensificar no pós-cirúrgico. O presente estudo teve como objetivo analisar a percepção e satisfação da imagem corporal de indivíduos pós-cirurgia bariátrica. Materiais e métodos: Trata-se de uma pesquisa do tipo transversal, quantitativa de caráter descritivo, cuja coleta foi realizada online através do Google Forms. A percepção e a satisfação quanto à imagem corporal foram investigadas através da Escala de Silhuetas para Cirurgia da Obesidade (ESCO). Os dados foram submetidos à análise descritiva para a caracterização da população estudada, foi realizada uma Matriz de Correlações e considerou-se o nível de significância de 5%. Discussão: De acordo com a Sociedade Brasileira de CB e Metabólica, mais de 70% das CBs realizadas no Brasil são feitas em mulheres, com média de idade entre 35 e 50 anos. Resultados e conclusão: A população estudada foi predominantemente do sexo feminino (90,2%) e a idade média foi de 37,8 anos. Quanto à percepção da imagem corporal, 29,4% dos participantes se classificaram com IMC menor que o atual calculado, em contrapartida 70,6% se percebiam com um IMC maior do que realmente possuíam. Os pacientes submetidos à CB permanecem insatisfeitos com sua imagem corporal e demonstram comportamento de risco para transtornos alimentares.

Chile is one of the fastest aging countries in Latin America, and the country is currently at an advanced stage of demographic transition. Projections highlight that that in another decade, Chile will emerge as an aging economy. Within the framework of the Fondecyt Regular 1201115 project: “Gender and Aging: An Ethnography on the Social and Moral Organization of Care in the Peñalolén commune (Santiago, Chile),” in this article, we address the findings of a case study on the social organization of elderly care in the Peñalolén commune (Metropolitan Region, Chile). We do so in conjunction with social and gender inequalities from a feminist perspective. The aim of the article is to analyze the social perceptions about aging held by professionals of municipal services working with the elderly population in this specific context. We conducted interviews with these workers using an ethnographic approach that integrated both digital and in-person methodological strategies, and subjected the information collected to a thorough discourse analysis using MaxQDA software (2001 version). The results reveal that the interviewed professionals’ perceptions of old age intermingle the definitions of old age derived from regulatory and public policy frameworks with their own personal and professional experiences in the communal territory. They also demonstrate the multidimensional nature of the inequalities faced by the elderly in Peñalolén, perceived by professionals as demands to be addressed in the exercise of their work. In sum, we propose a perspective of old age and aging that considers its complexity in terms of situated territorial experience by applying ethnographic listening with a gender perspective of the various actors working with the elderly individuals in each context.

Este artículo se centra en la temprana recepción de la literatura de James Macpherson en España. Se mencionan las traducciones de José Antonio Ortiz Rojo (1788) y de Pedro Montengón (1800) y se registran algunas referencias sobre la literatura osiánica en la prensa del momento. La parte central del trabajo investiga las traducciones de José Marchena consistentes en dos poemas completos («La guerra de Caros» y «La guerra de Inistona»), seis fragmentos (procedentes de «Los cantos de Selma», «Carrictura» y «Cartón») publicados en Variedades de Ciencias, Literatura y Artes en 1804 y otra composición completa extensa titulada «Beratón». Una vez clasificadas, se aborda la temática y se determina la forma de traducir del sevillano mediante sendos análisis traductológicos. Finalmente se mencionan otros autores posteriores a Marchena cuyas obras evidencian y refrendan el interés por la literatura osiánica en España.

RESUMO O artigo procura considerar a posição crítica de Graciliano Ramos em face do romance de 30, primeiro quanto às vertentes materialista e espiritualista e, depois, acerca dos motivos estéticos e políticos que levaram a nossa ficção à decadência. Na segunda parte do estudo, tenta-se compreender como o período sombrio, os últimos anos da década, impregna o ânimo do autor, cuja perspectiva forja uma nova técnica na escrita de Vidas secas.